ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project

Jarith L. Ebenau*, Tessa Timmers, Linda M.P. Wesselman, Inge M.W. Verberk, Sander C.J. Verfaillie, Rosalinde E.R. Slot, Argonde C. Van Harten, Charlotte E. Teunissen, Frederik Barkhof, Karlijn A. Van Den Bosch, Mardou Van Leeuwenstijn, Jori Tomassen, Anouk Den Braber, Pieter Jelle Visser, Niels D. Prins, Sietske A.M. Sikkes, Philip Scheltens, Bart N.M. Van Berckel, Wiesje M. Van Der Flier

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

ObjectiveTo investigate the relationship between the ATN classification system (amyloid, tau, neurodegeneration) and risk of dementia and cognitive decline in individuals with subjective cognitive decline (SCD).MethodsWe classified 693 participants with SCD (60 ± 9 years, 41% women, Mini-Mental State Examination score 28 ± 2) from the Amsterdam Dementia Cohort and Subjective Cognitive Impairment Cohort (SCIENCe) project according to the ATN model, as determined by amyloid PET or CSF β-amyloid (A), CSF p-tau (T), and MRI-based medial temporal lobe atrophy (N). All underwent extensive neuropsychological assessment. For 342 participants, follow-up was available (3 ± 2 years). As a control population, we included 124 participants without SCD.ResultsFifty-six (n = 385) participants had normal Alzheimer disease (AD) biomarkers (A-T-N-), 27% (n = 186) had non-AD pathologic change (A-T-N+, A-T+N-, A-T+N+), 18% (n = 122) fell within the Alzheimer continuum (A+T-N-, A+T-N+, A+T+N-, A+T+N+). ATN profiles were unevenly distributed, with A-T+N+, A+T-N+, and A+T+N+ containing very few participants. Cox regression showed that compared to A-T-N-, participants in A+ profiles had a higher risk of dementia with a dose-response pattern for number of biomarkers affected. Linear mixed models showed participants in A+ profiles showed a steeper decline on tests addressing memory, attention, language, and executive functions. In the control group, there was no association between ATN and cognition.ConclusionsAmong individuals presenting with SCD at a memory clinic, those with a biomarker profile A-T+N+, A+T-N-, A+T+N-, and A+T+N+ were at increased risk of dementia, and showed steeper cognitive decline compared to A-T-N- individuals. These results suggest a future where biomarker results could be used for individualized risk profiling in cognitively normal individuals presenting at a memory clinic.

Original languageEnglish
Pages (from-to)46-58
Number of pages13
JournalNeurology
Volume95
Issue number1
Early online date10 Jun 2020
DOIs
Publication statusPublished - 7 Jul 2020

Funding

The Article Processing Charge was funded by the authors. The Alzheimer Center Amsterdam is supported by Alzheimer Nederland and Stichting VUMC funds. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The clinical database structure was developed with funding from Stichting Dioraphte. The SCIENCe project is supported by a research grant from Gieskes-Strijbis fonds. W.M.v.d.F. holds the Pas-man chair. W.M.v.d.F. and P.J.V. received funding in the context of Deltaplan Dementie from ZonMW Memorabel (Netherlands Consortium of Dementia Cohorts [NCDC] project 73305095005) and Alzheimer Nederland. PET scans were funded by research grants from AVID and Piramal Neuroimaging. F.B. is supported by the University College London Hospitals NHS Foundation Trust Biomedical Research Center.

FundersFunder number
NCDC
Netherlands Organization of Scientific Research
Piramal Neuroimaging
Boehringer Ingelheim
EU Joint Programme – Neurodegenerative Disease Research
Avid Radiopharmaceuticals
Takeda Canada
ZonMw73305095005
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
University College London Hospitals NHS Foundation Trust

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